COVID-19 ups AIBD risk, but vaccination helps

Individuals with COVID-19 infection are at higher risk of autoimmune blistering disease (AIBD), but vaccination helps reduce such risk, suggests a study.

“Our study provides novel and robust evidence that COVID-19 vaccination is associated with a reduced risk of developing AIBD, while COVID-19 infection significantly increases this risk,” the authors said.

 COVID-19 infection showed a significant association with an increased AIBD risk (hazard ratio [HR], 1.508, 95 percent confidence interval [CI], 1.260–1.805). This risk is more noticeable for pemphigus (HR, 2,432, 95 percent CI, 1.618–3.657) than bullous pemphigoid (HR, 1.376, 95 percent CI, 0.1.019–1.857). [J Am Acad Dermatol 2025;92:452-463]

On the other hand, vaccination against COVID-19 correlated with nearly a 50-percent reduction in AIBD risk (HR, 0.514, 95 percent CI, 0.394–0.672), with the most significant risk decrease for pemphigus (HR, 0.477, 95 percent CI, 0.241–0.946).

Furthermore, a more than threefold increase in AIBD risk was observed in the infection cohort (HR, 3.130, 95 percent CI< 2.411–4.063), particularly for pemphigus (HR, 5.508, 95 percent CI, 2.973–10.205), when comparing between COVID-19 and vaccination.

“[T]he findings underscore the importance of vaccination not only in preventing severe COVID-19 outcomes but also in potentially protecting against autoimmune complications,” the authors said. “This potential dual benefit of vaccination should be a key message in public health campaigns and clinical practice to enhance vaccine uptake and ultimately improve health outcomes.”

Vaccination

The current findings support those of a previous investigation on several autoimmune outcomes following vaccination, which found no significant risk associations. [J Am Acad Dermatol 2023;89:685-693]

Vaccines have been shown to boost the immune system in a controlled manner, which potentially aids in maintaining immune homeostasis and reducing the likelihood of aberrant immune responses that could lead to autoimmunity. [Int J Immunopathol Pharmacol 2013;26:283-290; Vaccines (Basel) 2021;9:815]

"This is in stark contrast to the immune response elicited by natural infection, which can be more powerful and possibly dysregulated, including COVID-19,” the authors said. [Nat Rev Immunol  2019;19:383-397; Front Immunol 2020;11:2037]

“Our findings suggest that COVID-19 vaccines not only prevent severe outcomes related to the infection but also reduce the risk of subsequent autoimmune complications,” they added.

Autoimmune diseases

The findings on AIBD may extend to other autoimmune diseases, with growing evidence suggesting that COVID-19 may trigger various autoimmune conditions, such as multiple sclerosis and rheumatoid arthritis. [EClinicalMedicine 2023;63:102154]

Likewise, evidence from an emerging body of literature shows that vaccines, even those for COVID-19, offers protection against some autoimmune diseases. [EClinicalMedicine 2023;63:102154]

"This dual aspect of COVID-19's impact on autoimmunity—both as a trigger through infection and as a mitigator through vaccination—highlights the complex interplay between infectious agents and the immune system,” the authors said. 

The current population-based retrospective study used data from more than 112 million patients. The authors compared the risk of AIBD within 3 months among three cohorts: COVID-19 infection, COVID-19 vaccination, and controls. They also performed seven sensitivity analyses. 

This study was limited by its retrospective design and possible under-reporting of COVID-19 cases and vaccinations.